Efficacy and Tolerability of Viloxazine Extended-Release for Attention-Deficit/Hyperactivity Disorder in Adolescents and Adults: A Systematic Review With Qualitative Synthesis of All Studies and Meta-Analysis of Adolescent Data

Viloxazine extended-release (ER) is a non-stimulant medication approved for the treatment of attention-deficit hyperactivity disorder (ADHD) in pediatric and adult populations. While numerous randomized controlled trials (RCTs) have demonstrated its efficacy in young populations, evidence specific to adolescents remains limited, and even fewer data on adults exist. This systematic review and meta-analysis evaluates the efficacy and tolerability of viloxazine ER in adolescents and adults through a qualitative synthesis of all available studies and a meta-analysis of adolescent data. A literature search was conducted in January 2026 using PubMed, the Cochrane Library, Google Scholar, and ClinicalTrials.gov. Eligible studies included RCTs evaluating the efficacy of viloxazine ER in adolescent or adult populations diagnosed with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria. Three studies were included in the review. Quantitative meta-analysis was performed when at least two studies were available within the same population. Effect sizes were calculated as standardized mean differences using Hedges’ g under a random-effects model. Adult outcomes were summarized descriptively due to limited data. Risk of bias was assessed using the National Institute of Health (NIH) Study Quality Assessment Tool. Safety outcomes were assessed qualitatively. Three RCTs met the inclusion criteria. Two adolescent trials (n = 593) were pooled for meta-analysis. Viloxazine ER was associated with a statistically significant reduction in ADHD symptom severity in adolescents compared with placebo (Hedges’ g =-0.33, 95% CI -0.50 to -0.16) with no observed heterogeneity (I² = 0%). One adult RCT demonstrated statistically significant improvement in ADHD symptoms compared with placebo. Viloxazine ER was generally well tolerated with low discontinuation rates and mild adverse events. Viloxazine ER is associated with modest and consistent but statistically significant efficacy in reducing ADHD symptoms among adolescents, with a favorable tolerability profile. Although adult evidence is limited, the available data suggest that viloxazine ER is beneficial to this population as well. The findings overall support viloxazine ER as an effective non-stimulant pharmacotherapy option for adolescents with ADHD, particularly so when stimulant therapy is not tolerated. Further research should prioritize long-term outcomes and efficacy in adult populations.